Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/113819
DC Field | Value | Language |
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dc.contributor.author | Bessa, Cláudia | - |
dc.contributor.author | Loureiro, Joana B. | - |
dc.contributor.author | Barros, Matilde | - |
dc.contributor.author | Isca, Vera M. S. | - |
dc.contributor.author | Sardão, Vilma A. | - |
dc.contributor.author | Oliveira, Paulo J. | - |
dc.contributor.author | Bernardino, Raquel L. | - |
dc.contributor.author | Herman-de-Sousa, Carina | - |
dc.contributor.author | Costa, Maria Adelina | - |
dc.contributor.author | Correia-de-Sá, Paulo | - |
dc.contributor.author | Alves, Marco G. | - |
dc.contributor.author | Rijo, Patrícia | - |
dc.contributor.author | Saraiva, Lucília | - |
dc.date.accessioned | 2024-03-05T12:45:07Z | - |
dc.date.available | 2024-03-05T12:45:07Z | - |
dc.date.issued | 2023 | - |
dc.identifier.issn | 1422-0067 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/113819 | - |
dc.description.abstract | Metabolic reprogramming is a central hub in tumor development and progression. Therefore, several efforts have been developed to find improved therapeutic approaches targeting cancer cell metabolism. Recently, we identified the 7a-acetoxy-6b-benzoyloxy-12-O-benzoylroyleanone (Roy- Bz) as a PKC -selective activator with potent anti-proliferative activity in colon cancer by stimulating a PKC -dependent mitochondrial apoptotic pathway. Herein, we investigated whether the antitumor activity of Roy-Bz, in colon cancer, could be related to glucose metabolism interference. The results showed that Roy-Bz decreased the mitochondrial respiration in human colon HCT116 cancer cells, by reducing electron transfer chain complexes I/III. Consistently, this effect was associated with downregulation of the mitochondrial markers cytochrome c oxidase subunit 4 (COX4), voltage-dependent anion channel (VDAC) and mitochondrial import receptor subunit TOM20 homolog (TOM20), and upregulation of synthesis of cytochrome c oxidase 2 (SCO2). Roy-Bz also dropped glycolysis, decreasing the expression of critical glycolytic markers directly implicated in glucose metabolism such as glucose transporter 1 (GLUT1), hexokinase 2 (HK2) and monocarboxylate transporter 4 (MCT4), and increasing TP53-induced glycolysis and apoptosis regulator (TIGAR) protein levels. These results were further corroborated in tumor xenografts of colon cancer. Altogether, using a PKC -selective activator, this work evidenced a potential dual role of PKC in tumor cell metabolism, resulting from the inhibition of both mitochondrial respiration and glycolysis. Additionally, it reinforces the antitumor therapeutic potential of Roy-Bz in colon cancer by targeting glucose metabolism. | pt |
dc.language.iso | eng | pt |
dc.publisher | MDPI | pt |
dc.relation | This research was funded by financial support from national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through LAQV/REQUIMTE (UID/QUI/50006/2020), CBIOS (UIDB/04567/2020, UIDP/04567/2020), UMIB (UIDB/00215/2020, UIDP/00215/2020, LA/P/0064/2020), ITR (LA/P/0064/2020). Vera M. S. Isca (SFRH/BD/137671/2018); Marco G. Alves (2021.03439.CEECIND). Also, this work was financed by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01-0246-FEDER-000010 (Multidisciplinary Institute of Ageing, Coimbra) through the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia, under project[s] UIDB/04033/2020 and UIDB/04539/2020, UIDP/04539/2020 and LA/P/0058/2020. | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | Roy-Bz | pt |
dc.subject | PKCδ | pt |
dc.subject | anticancer agent | pt |
dc.subject | OXPHOS | pt |
dc.subject | glycolysis | pt |
dc.title | Counteracting Colon Cancer by Inhibiting Mitochondrial Respiration and Glycolysis with a Selective PKCδ Activator | pt |
dc.type | article | - |
degois.publication.firstPage | 5710 | pt |
degois.publication.issue | 6 | pt |
degois.publication.title | International Journal of Molecular Sciences | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.3390/ijms24065710 | pt |
degois.publication.volume | 24 | pt |
dc.date.embargo | 2023-01-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0001-7014-4614 | - |
crisitem.author.orcid | 0000-0002-5201-9948 | - |
Appears in Collections: | I&D CIBB - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
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Counteracting-Colon-Cancer-by-Inhibiting-Mitochondrial-Respiration-and-Glycolysis-with-a-Selective-PKC-ActivatorInternational-Journal-of-Molecular-Sciences.pdf | 2.9 MB | Adobe PDF | View/Open |
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